Researchers Take A Closer Look At Extended Revlimid-Dexamethasone Therapy For Newly Diagnosed Myeloma
Findings from a recent retrospective study conducted at the Mayo Clinic show that certain newly diagnosed myeloma patients can achieve deep responses and long-term disease control through extended treatment with Revlimid and dexamethasone.
Among a large sample of patients who were initially treated with Revlimid and dexamethasone after diagnosis – and who did not undergo an early stem cell transplant – one fifth received the two-drug therapy for more than three years.
Almost two thirds of these patients who were treated for more than three years achieved at least a very good partial response to treatment. In contrast, less than a quarter of the patients treated for less than three years achieved a very good partial response.
Patients who were treated for more than three years were less likely to have high-risk disease than patients who were treated for a shorter period of time, but they also took longer to achieve their best response to treatment than patients treated less than three years with the Revlimid (lenalidomide)-dexamethasone combination (6 months versus 4 months).
According to the investigators, the finding in regard to time to best response is in line with previous research, which has shown that patients with more aggressive forms of multiple myeloma tend to respond quickly to treatment, but are also more likely to relapse earlier.
Unfortunately, the retrospective nature of the study makes it difficult to pin down its implications. In part, the study simply provides insight into the characteristics of patients who respond for an extended period of time to treatment with Revlimid plus dexamethasone.
At the same time, one could argue that the study's findings support those who favor treatment with the Revlimid-dexamethasone combination for as long as patients can tolerate, and continue to respond to, the regimen.
Revlimid is one of the most commonly used agents for the treatment of newly diagnosed as well as relapsed and refractory myeloma patients.
Previous observational studies have shown that some newly diagnosed patients are able to achieve long-term responses with Revlimid, some of which last for several years.
In the current retrospective study, investigators sought to identify the characteristics of patients treated with Revlimid and dexamethasone over an extended period of time.
The researchers retrospectively analyzed data for a sample of 175 patients who were diagnosed with myeloma at the Mayo Clinic between 2003 and 2011.
To be included in the sample, patients had to receive Revlimid and dexamethasone as their initial treatment after diagnosis. Patients were excluded from the sample, however, if they received a stem cell transplant within a year of their diagnosis.
Revlimid was administered at a dose of 25 mg per day for 21 days out of a 28-day cycle.
During the early part of the period covered by the study, dexamethasone (Decadron) was administered at a dose of 40 mg on days 1-4, 9-12, and 17-20 of the 28-day cycle. Later in the period, however, the dose was reduced to 40 mg weekly.
The median patient age was between 65 and 66 years.
The researchers divided the patients into two groups based on how long they received treatment with Revlimid and dexamethasone: less than three years (81 percent), and more than three years (19 percent, or 33 patients). The latter group was referred to as “long-term responders” by the investigators.
The investigators found that the share of patients who achieved at least a very good partial response as their best response to the Revlimid-dexamethasone therapy was significantly larger among long-term responders compared to patients who received the two-drug combination for less than three years (64 percent versus 22 percent, respectively).
Interestingly, the median time to best response was longer for long-term responders (six months), compared to patients who received treatment for less than three years (four months).
The median progression-free survival was 102 months (8.5 years), and the median overall survival was not reached, for long-term responders.
Overall, 94 percent of the long-term responders were alive at a median follow-up time of 56 months (4.7 years).
The investigators also found that long-term responders were more likely to have standard-risk disease (64 percent) than patients who received the Revlimid-dexamethasone treatment for less than three years (44 percent).
Nineteen of the 33 of the long-term responders (58 percent) are still being treated with the Revlimid-dexamethasone combination. Among the 14 long-term responders who have stopped the therapy, only one patient did so for side effect-related reasons.
When the investigators looked at the data in their sample for patients who received the Revlimid-dexamethasone therapy for more than five years, they found that 83 percent of those patients achieved at least a very good partial response.
In addition, the median time to achieving best response was even longer in the "very-long-term responders" than in patients who received Revlimid-dexamethasone treatment for less than five years (nine months versus four months, respectively).
Implications Of The Study
The implications one can draw from the current study depend, to a significant extent, on what one can assume about why patients in the study were treated as long as they were.
If all patients in the study were treated with Revlimid and dexamethasone until they stopped responding to treatment, then the implications of the study are limited. It is mainly a description of differences in the characteristics of patients who respond to treatment for a long time, and those who do not.
If, on the other hand, there was some randomness to how long patients were treated, then the study could be interpreted as supporting long-term treatment with Revlimid and dexamethasone, because patients who were treated longer had better treatment outcomes.
Unfortunately, because this was a retrospective study, where a variety of factors could have affected why patients were treated as they were, one cannot know for certain why certain patients received treatment for a very long time, and others did not.
By choosing the label "long-term responders" to describe patients in the study who were treated for more than three years, the study authors favor the assumption that patients in the study were typically treated for as long as they kept responding to treatment.
That assumption is not really supported, however, by all the data the authors report. In their article, for example, the authors report that patients who were treated for less than three years were treated for a median of just 7 months.
Given how long newly diagnosed myeloma patients typically respond to Revlimid-dexamethasone therapy, it is unlikely that a failure to continue responding to treatment was the reason these patients stopped treatment after such a relatively short period of time.
Thus, it would appear that there was, in fact, at least some randomness to why some patients in the study were treated for a relatively short amount of time, and others for a longer period of time.
And that, in turn, indicates that the study can be seen as providing support for those who argue that newly diagnosed myeloma patients treated with Revlimid and dexamethasone should be treated for extended periods of time.
For more information, please refer to the study in the journal Leukemia (no abstract available; study published as a "letter to the editor"). Additional information about the sample of patients analyzed in the current study can be found in an article published earlier last year, also in the journal Leukemia (abstract; pre-publication draft available in its entirety here).
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